The specific aims of the proposed project are to continue the studies on the production, isolation-separation, differentiation, structural-elucidation and modification, and the biogenesis of various polyene macrolide antifungal antibiotics. In particular, the investigations will emphasize the clinically-important heptaene macrolides including the non-aromatic heptaene macrolides, amphotericin B and the candidin complex, and the aromatic heptaene macrolides, candicidin, levorin, candimycin and partricin. Lesser emphasis will be given to the tetraene macrolide complex, nystatin, and the hexaene macrolide complexes mediocidin and endomycin. The technique of high speed liquid chromatography recently developed for the analysis of polyene macrolide compositions will be employed for the preparative separation of these polyene macrolide complexes. Preliminary investigations with isolated pure components will involve chemical degradative procedures. Physical studies involving mass spectrometry and NMR spectroscopy will also be carried out. With the isolation of pure polyene macrolide components, the preparation of crystalline heavy atom derivatives will be followed by single crystal x-ray analyses employed so successfully in our laboratories for the elucidation of the total molecular structure of amphotericin B. The molecular interaction of polyene macrolides with sterols and steroid derivatives will also be the subject of continued investigation. Previously described novel pharmacological-biochemical properties of oral polyene macrolide administration as related to sterol interaction have increased the importance of these antibiotics in medicine, particularly in the areas of cholesterol-lipid metabolism, prostatic hypertrophy and atherosclerosis.